A prospective, randomized control study comparing the analgesic efficacy of continuous infusion of local anesthetic versus intermittent bolus through thoracic paravertebral cathetrisation in patients undergoing elective thoracotomy surgeries

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“A PROSPECTIVE, RANDOMIZED CONTROL STUDY COMPARING THE ANALGESIC EFFICACY OF CONTINUOUS INFUSION OF LOCAL ANESTHETIC VERSUS INTERMITTENT BOLUS THROUGH THORACIC PARAVERTEBRAL CATHETRISATION IN PATIENTS UNDERGOING ELECTIVE THORACOTOMY SURGERIES”

Dissertation submitted to

THE TAMIL NADU DR. M.G.R. MEDICAL UNIVERSITY In partial fulfillment for the award of the degree of

DOCTOR OF MEDICINE IN

ANAESTHESIOLOGY BRANCH X

INSTITUTE OF ANAESTHESIOLOGY AND CRITICAL CARE MADRAS MEDICAL COLLEGE

CHENNAI- 600003 APRIL 2016

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CERTIFICATE

This is to certify that the dissertation entitled, “A PROSPECTIVE, RANDOMIZED CONTROL STUDY COMPARING THE ANALGESIC EFFICACY OF CONTINUOUS INFUSION OF LOCAL ANESTHETIC VERSUS INTERMITTENT BOLUS THROUGH THORACIC PARAVERTEBRAL CATHETRISATION IN PATIENTS UNDERGOING ELECTIVE THORACOTOMY SURGERIES” submitted by Dr. S. DINESH KUMAR, in partial fulfillment for the award of the degree of Doctor of Medicine in Anaesthesiology by the Tamil Nadu Dr. M.G.R. Medical University, Chennai., is a bonafide record of the work done by him in the INSTITUTE OF ANAESTHESIOLOGY AND CRITICAL CARE, Madras Medical College and government hospital, during the academic year 2013-2016.

Prof. DR. B.KALA M.D., D.A., DR. R.VIMALA M.D.

PROFESSOR AND DIRECTOR, DEAN,

INSTITUTE OF ANAESTHESIOLOGY MADRAS MEDICAL COLLEGE &

AND CRITICAL CARE, GOVT. GENERAL HOSPITAL

MADRAS MEDICAL COLLEGE, CHENNAI -600003 CHENNAI -600 003.

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CERTIFICATE BY THE GUIDE

This is to certify that the dissertation entitled, “A PROSPECTIVE, RANDOMIZED CONTROL STUDY COMPARING THE ANALGESIC EFFICACY OF CONTINUOUS INFUSION OF LOCAL ANESTHETIC VERSUS INTERMITTENT BOLUS THROUGH THORACIC PARAVERTEBRAL CATHETRISATION IN PATIENTS UNDERGOING ELECTIVE THORACOTOMY SURGERIES” submitted by Dr. S. DINESH KUMAR, in partial fulfilment for the award of the degree of Doctor of Medicine in Anaesthesiology by the Tamil Nadu Dr. M.G.R. Medical University, Chennai., is a bonafide record of the work done by him in the INSTITUTE OF ANAESTHESIOLOGY AND CRITICAL CARE, Madras Medical College and government hospital, during the academic year 2013-2016.

Prof .DR .M.VELLINGIRI M.D., D.A

Professor of Anaesthesiology, Institute Of Anaesthesiology& Critical Care,

Madras medical college & Govt. General Hospital Chennai- 600 003

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DECLARATION

I hereby, solemnly declare that this dissertation entitled “A PROSPECTIVE, RANDOMIZED CONTROL STUDY COMPARING THE ANALGESIC EFFICACY OF CONTINUOUS INFUSION OF LOCAL ANESTHETIC VERSUS INTERMITTENT BOLUS THROUGH THORACIC PARAVERTEBRAL CATHETRISATION IN PATIENTS UNDERGOING ELECTIVE THORACOTOMY SURGERIES” is a bonafide record of the work done by me in the Institute of Anaesthesiology and Critical Care, Madras Medical College and Government General Hospital, Chennai, during the period 2013 – 2016 under the guidance of DR. M.VELLINGIRI, M.D., D.A., Professor, Institute of Anaesthesiology and Critical Care, Madras Medical College, Chennai – 3 and submitted to The Tamil Nadu Dr. M.G.R. MedicalUniversity, Guindy, Chennai – 32, in partial fulfilment for the requirements for the award of the degree of M.D.

Anaesthesiology (Branch X), examinations to be held on April 2016.

I have not submitted this dissertation previously to any university for the award of degree or diploma.

Place: Chennai Dr.S. DINESH KUMAR

Date:

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ACKNOWLEDGEMENT

I am extremely thankful to DR.R.VIMALA M.D., Dean, Madras Medical College &

Rajiv Gandhi Govt. General Hospital, for her permission to carry out this study.

I am immensely grateful to Prof. DR. B.KALA, M.D., D.A., Director, Institute of Anaesthesiology and Critical Care, for her concern and support in conducting this study.

I am extremely grateful and indebted to my guide Prof .DR M..VELLINGIRI M.D.

, D.A, Professor of Anaesthesiology, Institute of Anaesthesiology& Critical Care, for his concern, inspiration, meticulous guidance, expert advice and constant encouragement in preparing this dissertation.

I am extremely thankful to my Assistant Professors especially DR.R.MALA MD., DA, DR.M.VIJAYASHANKAR MD., DR. R. SUMATHY DA, DR.P.RAVI MD., for their guidance and expert advice in carrying out this study.

I am thankful to the Institutional Ethical Committee for their guidance and approval for this study.

My sincere thanks to the statistician, who played an important role during my study.

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I am thankful to all my colleagues, family and friends for their moral support, help and advice in carrying out this dissertation.

Last but not the least; I thank all the patients for willingly submitting themselves for this study.

Above all I pay my gratitude to the Lord Almighty for blessing me to complete this work.

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CONTENTS

S.NO

TOPIC

PAGE NO.

1 INTRODUCTION 1

2 AIM OF THE STUDY 2

3 THORACOTOMY & VARIOUS MODES OF ANALGESIA 3

4

ANATOMY & PATHOPHYSIOLOGY OF PAIN IN THORACIC

SURGERY 10

5 PHARMACOLOGY OF BUPIVACAINE 17

6 REVIEW OF LITERATURE 20

7 MATERIALS AND METHOD 23

8 OBSERVATION AND RESULTS 29

9 DISCUSSION 91

10 SUMMARY 95

11 CONCLUSION 96

12 BIBLIOGRAPHY

13 ANNEXURES

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AIM OF THE STUDY:

To compare the analgesic efficacy of thoracic paravertebral block using continuous infusion of local anesthetic versus intermittent bolus in patients undergoing elective thoracotomy surgeries

BACKGROUND:

Various techniques and drug regimens for thoracic paravertebral block have been evaluated for post-thoracotomy analgesia. In this study continuous

infusion versus intermittent bolus of local anesthetics for thoracic paravertebral block have been compared in the patients undergoing elective thoracotomy surgeries. 64 patients have been selected and randomized in to two groups with 32 patients in each group. Paravertebral block was performed and catheter kept in the paravertebral space. Intra operative vitals were noted. Post operative vitals and Visual Analogue Score were observed and compared between the two groups.

RESULTS:

Systolic blood pressure, diastolic blood pressure and mean arterial pressure

were lower in continuous infusion group than the intermittent bolus group

during both intra operatively and post operatively which is statistically

significant.

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The visual analogue scale score post-operatively was meaningfully less in continuous infusion intervention group compared to intermittent bolus

intervention group by 0.29 mean score points which is statistically significant.

CONCLUSION:

From this study we can conclude that continuous infusion of local anesthetic is really superior to intermittent bolus administration of local anesthetic in the paravertebral block as shown by continuous pain relief with absence of break through pain and better patient compliance in post operative physiotherapy and ablility to cough out sputum.

KEY WORDS:

Analgesia, paravertebral block, thoracotomy surgeries, local anesthetics

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INTRODUCTION

One of the most painful surgical incision is the Thoracotomy incision. The reduction in FRC and the ability to take a deep breath and cough out sputum after Thoracotomy are greatly influenced by pain. These patients may not be able to clear the secretion even if they willing to, because of the pain. This may end up in atelectasis and finally pneumonia. The associated cardiac complications are also less if we provide adequate analgesia to the patient¹.

The lateral thoracotomy incision is very painful. The intensity of pain depends on the site and extent of the incision. Intercostal nerve disruption and the pleura and chest wall inflammation contribute to the discomfort. The location and number of the chest drainage also contribute to the pain. Few patients may get shoulder pain following thoracotomy surgeries²⁹.

Though thoracic epidural technique is considered as the gold standard for the pain relief in thoracotomy surgeries. Thoracic paravertebral block has been gaining much attention these days because of its numerous advantages over thoracic epidural techniques.

Paravertebral space was described in the early part of twentieth century. Hugo sellheim of Leipzig successfully demonstrated Paravertebral block for the first time in 1905²⁴. Initially this technique was performed to describe the pain pathways of abdominal and thoracic region by Arthur Lawen. As it provides adequate unilateral pain relief with cardiovascular stability, this technique was widely used for lobectomy and thoracoplasty in Tuberculosis patients.

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AIM OF THE STUDY

To compare the analgesic efficacy of thoracic paravertebral block using continuous infusion of local anesthetic versus intermittent bolus in patients undergoing elective thoracotomy surgeries

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THORACOTOMY

Thoracotomy incision has been used for following surgeries:

 CMC for stenotic mitral valve

 Lobectomy

 Pneumonectomy

 Occasionally for esophageal perforation repair

IMPORTANCE OF PAIN CONTROL IN THORACOTOMY SURGERY:

The importance of adequate pain management in the thoracic surgical patient cannot be overstated. Inadequate pain control in these high risk patients will results in

 Splinting,

 Poor respiratory effort and

 Inability to cough and clear secretions

All the above ultimately ends with airway closure, atelectasis, shunting and hypoxemia.

In addition acute pain increases sympathetic tone thereby causing tachycardia, hypertension, increasing myocardial oxygen demand, increased after load, myocardial dysfunction and arrhythmias.

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It also delays mobilisation resulting in DVT and pulmonary embolism. It also increases ICU stay and overall hospital expenses. Hence there should be a proper plan for managing pain post operatively.

PAIN

SPLINTING

UNABLE TO CLEAR SECRETIONS

ATELECTASIS

SHUNTING

HYPOXEMIA

SYMPATHETIC TONE

MYOCARDIAL O2

DEMAND

AFTERLOAD

ARRYTHMIAS

BED RIDDEN

DVT

HOSPITAL STAY

ECONOMY

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MODES OF ANALGESIA PARENTERAL ANALGESICS

OPIOIDS – PROS & CONS:

A balance between drug induced respiratory suppression and adequate analgesia in patients with already compromised lung is quite a challenging task with opioids as the sole analgesic.

If at all used as sole analgesic, parenteral opioids can be given through PCA. Due to high intensity of pain, ultimately patient may require high dose of opioids which increases the risk of PONV and respiratory depression. Prolonged use of high dose may even cause dependency.

NSAID:

NSAID as sole analgesic for thoracotomy pain relief will be insufficient. It can be used in combination with opioids, thereby reducing the overall opioids requirement by 30%²⁵. It reduces the post operative inflammation. NSAIDs are useful in treating the ipsilateral shoulder pain that is often present post operatively and is poorly controlled with epidural analgesia²⁵

It may cause platelet dysfunction and thereby increase bleeding tendency. They may also cause kidney injury, gastric erosion and increased bronchial reactivity

Acetaminophen is an antipyretic/analgesic with COX inhibition and can be administered orally or rectally in the dose of up to 4g/day. It reduces shoulder pain and has low toxicity compared with more potent COX-inhibiting NSAIDs¹⁵.

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KETAMINE:

Low-dose intramuscular ketamine (1mg/kg) is equivalent to the same dose of meperidine and cause less respiratory depression. It can also be given as low dose intravenous infusion and maybe useful in patients who are refractory to other therapies or if there is a contra indication to more common techniques⁵. The possibility of its psychomimetic effects are of concern in its regular use.

DEXMEDETOMIDINE:

It’s a selective adrenergic alpha 2 agonist has been reported as a useful adjunt for post thoracotomy analgesia. It is associated with hypotension, but it seems to preserve renal function.

LOCAL ANESTHETICS / NERVE BLOCKS:

INTERCOSTAL NERVE BLOCKS:

Advantages

 Blocking the intercostal nerves supplying the dermatomes of surgical incision is an effective method of providing analgesia for thoracotomy surgeries. It can be done percutaneously or under direct vision when the chest is open.

 Single shot intercostal block with local anesthetics may provide adequate pain relief for extubation.

Disadvantages

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 The duration of analgesia is restricted to the duration of action of the local anesthetic used. Also Indwelling intercostal catheters are difficult to position percutaneously

 Intercostal vessels lie close to the nerves and inadvertent injection of local anesthetic in to the vessels may precipitate local anesthetic toxicity.

 This block is associated with maximum risk of local anesthetic toxicity. Hence total Bupivacaine dose for a single time block should not exceed 1mg/kg²⁵. INTRAPLEURAL ANALGESIA

The effectiveness of this block depends on the patient position, infusion volume, chest drain and the type of surgery.Local anesthetic infusion through the catheter placed in the surgical wound at the time of closure will reduce the opioids requirement post operatively.

EPIDURAL ANALGESIA:

Epidural analgesia is considered as gold standard for thoracotomy surgeries.

Advantages

 Excellent and continuous pain relief

 Avoidance of parenteral opioids side effect.

Disadvantages

 Requires technical expertise

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 Hemodynamic instability due to sympathetic blockade.

 Technique cannot be performed in the presence of coagulopathy.

 Dural tap

PARAVERTEBRAL BLOCK:

Though it was initially used for providing post operative analgesia in the first half of twentieth century, later it extends to provide pain relief for angina pectoris, thigh bone fracture, cancer pain and rest pain. Herpes zoster neuralgia, renal colic and pain due to cholelithiasis were also treated with this technique¹⁰. Paravertebral block technique was also utilized for the management of supraventricular tachycardias.

Later, improvements in general anesthetic agents and techniques and the entry of thoracic epidural slowly replaced the Paravertebral block.

Eason and Wyatt re-explored Thoracic Paravertebral block by introducing a catheter in paravertebral space which allows repeated injections of local anesthetic agents and provide analgesia for a longer period than single time injection⁹.

With the advent of infusion pumps and the concern for local anesthetics toxicity, use of continuous infusion of low dose local anesthetics has been gaining popularity among the Anaesthesiologist. Continuous infusion techniques also helps to maintain constant pain relief and better patient compliance.

Paravertebral blocks are considered as the “unilateral epidurals,” as they block the spinal nerves on the side of anesthetic application, although they also have the potential for epidural spread (they can be bilateral if desired)¹⁹.

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CRYOANALGESIA

Cryoanalgesia probe maybe used intraoperatively to freeze the intercostals nerves and produce long duration of analgesia because the nerve regeneration after cryoneurolysis may take nearly one month. Onset of analgesia is typically prolonged to 24 to 48 hrs after cryoneurolysis¹⁶.

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ANATOMY AND PATHOPHYSIOLOGY OF PAIN IN THORACIC SURGERY

Nociceptive receptors transmits pain via C and A∆ fibres, which can be considered in three routes

 Intercostal nerves carry impulses from skin and intercoastal muscles

 Vagus nerves carry stimuli from lung and mediastinum. Visceral pain is sensitive to stretch only.

 Parietal pleura is highly sensitive to noxious stimulus. Latissmusdorsi and serratus anterior are supplied by thoracodorsal and long thoracic nerves respectively. Chest wall muscles involved in Thoracotomy are Latissmusdorsi, Serratus anterior, Pectorais major and Intercostal muscles

FACTORS AFFECTING ANALGESIC OUTCOME AFTER THORACOTOMY

 Surgical technique

 Choice of anesthetic modality

 Post operative level of care

 On going input from acute pain and physiotherapy

 Patient factors

 Psychological

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ANATOMY OF PARAVERTEBRAL SPACE

The Thoracic Paravertebral space starts from T1 and ends at T12. Its wedge shaped in all three dimensions.

Medially bounded by vertebral body, intervertebral disc and intervertebral foramina¹. Anterolaterally bounded by parietal pleura and innermost intervertebral membrane¹. Posteriorly bounded by transverse process of vertebra, heads of ribs and superior costotransverse ligament¹.

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21 The paravertebral space is divided into anterior subserous compartment and posterior sub endo thoracic compartment¹.

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22 The contents of the Paravertebral space are spinal nerves, white and Grey rami communicans, sympathetic chain, intercoastal nerves and fat²⁶.

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PREPARATION

After obtaining the informed consent, patient is shifted into operation theatre and the following monitors are connected. Non invasive blood pressure cuff, Pulse Oximeter probe, ECG chest leads. A wide bore i.v cannula is placed. Once he resuscitation cart and trained staff are available, procedure can be started. Patient is positioned with head and back flexed in the lateral position with the operative side on top.

TECHNIQUE:

18g tuohy needle is used. Under strict aseptic condition, the spinous processes are palpated and marked. About 2.5cm lateral to midline, skin is infiltrated with 1%

Lignocaine and the needle is entered to hit the transverse process at around 3-6cm.

Once transverse process is hit, needle is walked over it inferiorly just to pierce the superior costotransverse ligament and feeling for change in resistance once the paravertebral space is reached. Then the epidural catheter is threaded inside the space, keeping 4 to 5cm catheter inside the space. After 1% Lignocaine infiltration in the skin near the point of needle entry, tunnel is created and the catheter is fixed. Patient is turned back to supine position.

INDICATIONS:

 Thoracic surgery

 Fracture ribs

 Neuropathy

 Refractory angina pectoris

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 Relief of cancer pain

 Control of hyperhydrosis.

CONTRAINDICATIONS

 Patient refusal

 Local anaesthetic allergy

 Severe coagulopathy

 Local sepsis

 Tumors in the paravertebral space

 Severe deformity of spine

 Ipsilateral diaphragmatic palsy¹

 Patients depending on intercoastal muscles for respiration

COMPLICATIONS:

 Failure in inexperienced hands

 Inadvertent pleural puncture

 Pneumothorax

 In bilateral block epidural spread is more common when medial injections are given

 Ipsilateral horners syndrome

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ADVANTAGES OF PVB OVER EPIDURAL¹:

 Easier to perform

 Fewer failed blocks

 Decreased risk of neuraxial hematomas

 Analgesia is comparable with epidural in terms of success and efficacy

 Can be performed in anaesthetized patient

 Less neurological problems

 No hypotension

 No urinary retention

 Less sedation, nausea, vomiting, constipation compared to opioids usage in epidural

ADVANTAGES OF PVB OVER INTRA PLEURAL BLOCK¹:

 It produces less serum LA concentration

 Reduce chronic pain by intense block of sympathetic nerves

 Reduced tumor recurrence

 Less morbidity

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PHARMACOLOGY OF BUPIVACAINE

Bupivacaine is a long acting local anaestheticbelonging to amide group. Mepivacaine, Bupivacaine and Ropivacaine are characterized as pipecoloxylidides¹⁶. Addition of butyl group to the piperidine nitrogen of mepivacaine results in bupivacaine, which is 35times more lipid soluble and has potency and duration of action 3 to 4 times that of mepivacine²⁷.

MECHANISM OF ACTION

Local anesthetics bind to specific sites in voltage gated Na⁺current, thereby reducing excitability of neuronal, cardiac or central nervous system tissue¹⁷. Local anesthetics prevent transmission of nerve impulses (conduction blockade) by inhibiting passage of sodium ions through ion selective sodium channels in nerve membranes³. The sodium channel itself is a specific receptor for local anesthetic molecules. Failure of an increase in sodium channel ion permeability slows the rate of depolarization so that threshold potential is not reached and hence action potential is not reached²⁷. Local anesthetics does not alter the resting transmembrane potential or threshold potential METABOLISM

Possible way of metabolism of Bupivacaine include aromatic hydroxylation, N- dealkylation, amide hydrolysis and conjugation²⁰. Only the N-dealkylated metabolite N-desbutylbupivacaine, has been measured in blood or urine after epidural or spinal anesthesia²⁰. The mean total urinary excretion of Bupivacaine and its dealkylation and hydroxylation metabolites account for >40% of total anesthetic dose²⁰. Alpha 1- acid glycoprotein is the most important plasma protein binding site of Bupivacaine and its

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concentration is increased in many clinical situations, including post operative trauma⁶.

Bupivacaine has slow onset of action with average duration of action after infiltration ranges from 240 to 480 seconds⁸. Maximum single dose for infiltration is around 175mg and the Bupivacaine toxicity features manifest if the plasma concentration exceeds 3mcg/ml⁸. pK of Bupivacaine is 8.1 and it is 95% protein bounded⁸.

USES

 Topical anesthesia

 Local infiltration

 Peripheral nerve blockade

 Neuraxial anesthesia

 Paravertebral anesthesia

SIDE EFFECTS

 Allergy to Bupivacaine

 Cardiotoxicity – Precipituous hypotension, cardiac dysrhythmias and atrio- ventricular blocks². Premature ventricular contractions, widening of QRS complexes and ventricular tachycardias are the most common arrhythmias seen, though other arrhythmias including supraventricular tachycardia, atrio- ventricular block and ST-T wave changes can also occur but are less

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common¹⁴. Cardiotoxic plasma concentration of Bupivacaine are 8 to 10mcg/ml²⁸.

 Neurotoxicity – vertigo, tinnitus, twitching, slurred speech and seizures

 Hepatotoxicity

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REVIEW OF LITERATURES

1. Richardson J et al²³in 1994 concluded that rise in plasma cortisol after the surgery was significantly low in paravertebral block and the respiratory function is preserved.

2. Catale E et al⁴in 1996 did a study in anesthesiology and pain clinic department in Spain to determine the quality of continuous infusion versus bolus infusion of Bupivacaine after Thoracotomy. It is a prospective randomized controlled study done in 30 patients. The patients were given either a loading dose of 15ml of 0.375%

Bupivacaine and an infusion of 5ml of 0.25% Bupivacaine every hour or 20ml of 0.375% Bupivacaine every 6hours.

Pain intensity was assessed at rest and continuously at intervals of 1, 4, 10, 20 and 48 hours by VAS. The vitals, need of rescue analgesia or higher dose Bupivacaine and level of blockade were noted. In both the groups Bupivacaine toxicity did not occur.

At the end it was found that continuous infusion offers a better analgesia than bolus dose in post thoracotomy

3. Joshi GP et al¹²in 2008 conducted a study evaluating the role of regional technique for post thoracotomy analgesia which concluded that continuous Paravertebral block provided analgesia as equivalent to epidural but lesser incidence of hypotension. Also the incidence of pulmonary complication were less with paravertebral block than systemic analgesia

4, Kotzeet al¹in 2009 did a metaanalysis to review and metaregression to compare the heterogeneous trials between various groups. They compared the 48hours post

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operativeanalgesia in thoracotomy patients with continuous infusion or intermittent bolus of local anesthetics with or without additive in paravertebral block.

Pleural and muscular damage, intercostal nerve damage and costovertebral joint disruption causes pain in post operative thoracotomy patients. So it was found that optimal analgesia can be provided by multimodal approach like simple analgesics, systemic opioids, nerve blocks etc.

From their study, it was found that 50% decrease in post thoracotomy pain is obtained from higher dose of local anesthetics. So paravertebral block is an additional mode of analgesia to systemic opioids. But addition of opioid in paravertebral block did not offer any advantage. Also clonidine was also not effective. Single injection technique had unpredictable outcome though it was safe. Multiple injection technique was showing good outcome.

The risk of local anesthetic toxicity was balanced against by the improved analgesia and pulmonary mechanics from the higher local anesthetics doses. Toxic level of Bupivacaine was achieved when >0.5mg/kg/hour was given and/or when 0.25mg/kg/hour infusion used for 24hours.

5. De Cosmo G et al⁷in 2009 suggested continuous infusion of paravertebral block when thoracic epidural is contra-indicated or couldn’t be performed. Whereas the other techniques are not as effective alternative as that of paravertebral block.

6. Norum HM et al¹⁸in 2010 argued that epidural which was compared with paravertebral block were not optimally performed as they found catheter in thoracic epidural were kept too low.

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7.Pintaric TS et al²¹in 2011 concluded that paraertebral block is associated with lesser incidence of side effects, requires only fewer nursing staff and minimal monitoring than thoracic epidural.

8, According to Pipanmekapom et al²²in 2012, the use of continuous thoracic paravertebral block which was done under direct vision is found superior to thoracic epidural in difficult to access cases. It also offered less complications.

9, Kevin king et al¹³ in his review in 2012 states that thoracic epidural results in frequent difficulty in placing the catheter and failures when compared with paravertebral block. Also epidural is contraindicated in patients on anticoagulants. But not so in case of paravertebral block. Moreover paravertebral block does not cause hypotension and urinary retention as it does with epidural. It also required less monitoring and nursing care. So patients can be admitted in non-ICU units.

Paravertebral block also aids in neurological assessment despite providing analgesia and improved respiratory mechanics when compared to epidural blockade.

10, Gonulsagiroluet al¹¹in 2013 also says that though thoracic epidural and paravertebral block offers adequate analgesia for post thoracotomy cases, paravertebral blocks are easier and quicker to place technically and free of hypotension.

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MATERIALS AND METHOD

After getting approval from our institution’s ethics committee, this study was conducted among 64 patients belonging to ASA grade I and II who undergoes for elective thoracotomy surgery under general anaesthesia. The age of distribution was selected between 18 and 50 years with BMI ranging between 18 and 30 kg/m². All patients have undergone thorough preoperative examination.

The procedure was explained to the patient in their own language and consent was obtained. All patients underwent full examination like height, weight vitals like blood pressure, pulse rate and basic investigations like complete blood count which includes Hb and Platelets, renal function test that includes random blood sugar, blood urea nitrogen and serum creatinine, chest Xray and ECG. All major systems were examined and airway examination was also done. Visual Analogue Scale was explained to the patient with pictorial representation.

INCLUSION CRITERIA:

 Age : between 18 and 50 years

 BMI : between 18 and 30 kg/m²

 ASA: I and II

 Surgery : elective

 Mallampatti score: I and II

 Who have given valid informed consent

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EXCLUSION CRITERIA:

 Patient’s refusal

 Allergy to Local anaesthetics

 Coagulopathy

 Thoracic vertebral disease or deformity

 Systemic or local sepsis

 H/O seizures and any neurological deficit

 Psychiatric diseases

 Those patients not satisfying inclusion criteria

MATERIALS USED

 18G Tuohy needle, epidural catheter

 Loss of resistance syringe

 10ml syringe

 1% Lignocaine preparation for skin infiltration

 Drugs – 0.25% Bupivacaine

 Continuous infusion syringe pump system

 Sterile drapes

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 Monitors – ECG, NIBP, SPO2, EtCO2

 Visual analogue scale

Each patient have been randomly assigned into one of the two groups.

GROUP A:

Thirty two patients in this group received initial dose of 8ml of 0.25% Bupivacaine followed by continuous infusion at the rate 0.1ml/kg/hr of 0.25% Bupivacaine for up to 24 hours after the procedure.

GROUP B:

Thirty two patients in this group received the initial dose of 8ml of 0.25%

Bupivacaine followed by intermittent bolus of 0.1ml/kg of 0.25% Bupivacaine hourly for 24 hours after the procedure.

After obtaining the informed consent patients were shifted inside the operation theatre and the monitors were connected. Intra venous access was obtained with 16G intravenous cannula. Patients were turned to lateral position with the operating side on top. The patients were made to bend their back and bring their knees to chest. This position was maintained by an assistant. The back was painted with povidone iodine and draped with sterile towels. Under strict aseptic precautions, thoracic spine was palpated and a skin wheel was created at 2.5cm lateral to T5 Thoracic spine with 1%

Lignocaine. Tuohy needle was inserted till it hits the corresponding transverse process and then its walked over inferiorly and angulated slightly laterally. A change in resistance was felt when the needle pierces superior costotransverse ligament using

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loss of resistance syringe. Epidural catheter was inserted through the needle. After adequate skin infiltration with 1% Lignocaine tunneling was done and catheter passed through it and fixed. Patient turned to supine position. 8ml of 0.25% Bupivacaine was given through the catheter after negative aspiration for blood and csf.

Patients were premedicated with 1.5mg of inj. Midazolam, 2mcg/kg of inj. Fentanyl and 0.2mg of inj. Glycopyrrolate. Induction was done with Inj. Thiopentone sodium 5mg/kg and Inj. Vecuronium 0.1mg/kg. Inj. Lignocard 1.5mg/kg was given 90seconds before intubation to attenuate the stress response. Patients were then intubated with appropriate sized double lumen tube and the position is confirmed and fixed. Bladder were catheterized and the surgery started after proper positioning.

Anesthesia was maintained with 1% Sevoflurane along with O2 40% and N2O 60%.

Group A patients received continuous infusion of 0.25% Bupivacaine at the rate of 0.1ml/kg/hour, whereas the Group B patients received an intermittent bolus of 0.1ml/kg of 0.25% Bupivacaine for up to 24 hours post operatively.

After the surgery is over, patients were turned supine and the volatile agents were cut off and ventilation was assisted. Once the arterial blood gas reports were within normal range and patients had recovered adequately from the neuromuscular blockade, they were reversed with inj. Glycopyrrolate 20mcg/kg/min and inj.

Neostigmine 50mcg/kg. After adequate oral suctioning, patient was extubated. Visual analogue scoring was recorded.

Hypotension was defined as MAP declining 30% from its baseline value

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Paravertebral block was considered as a failure if patient experiences pain of VAS more than 4 and they were given rescue analgesia of inj. Tramadol 100mg. They were excluded from the study. All the patients were kept in post operative intensive care units. Intra operatively Patient’s heart rate and blood pressure were noted for every 5 minutes till first hour and then for every 30 minutes till eight hours and then hourly till 24hour postoperative period. Post operatively VAS score was noted for every 30 minutes till 8 hours and then hourly till 24 hours postoperatively. Analgesia was considered as adequate when VAS score ranges from 0 to 4. And inj. Tramadol was given for rescue analgesia. Other complications of Bupivacaine were also closely monitored.

The following parameters were monitored:

VITALS:

Heart rate, systolic blood pressure, diastolic blood pressure and mean blood pressure and VAS score

VAS SCORE:

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37

SIDE EFFECTS:

Reduction in MAP of >30% of baseline is considered as hypotension and is treated with i.v. fluids and titrated dose of inj.ephedrine 6mg.

Fall in heart rate to 40/min was considered as bradycardia and treated with inj.

Atropine 0.6mg

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38

OBSERVATION AND RESULTS

GROUPS

Groups Intervention Used Study Subjects

Continuous Infusion Group

 Pre operative paravertebral block with continuous infusion

of Bupivacaine Patients undergoing elective thoracotomy surgeries

Intermittent Bolus Group

 Pre operative Paravertebral block with intermittent bolus of Bupivacaine.

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39

Statistics

Descriptive statistics was done for all data and suitable statistical tests of comparison were done. Continuous variables were analysed with the unpaired t test and categorical variables were analysed with the Chi-Square Test and Fisher Exact Test.

Statistical significance was taken as P < 0.05. The data was analysed using EpiInfo software (7.1.0.6 version; Center for disease control, USA) and Microsoft Excel 2010.

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40

Sample Size Calculation

Sample size was determined based on

Study

Postoperative pain relief using intermittent intrapleural analgesia following thoracoscopic anterior correction for progressive adolescent idiopathic scoliosis

,

Authored by

Stephen AC Morris, et al

Published in

Scoliosis 2013, 8:18

In this study Pain scores significantly decreased following the administration of a bolus (p < 0.0001), with the mean pain score decreasing from 3.66 to 1.83 ( 50%

reduction)

(43)

41

Description:

• The confidence level is estimated at 95%

• with a z value of 1.96

• the confidence interval or margin of error is estimated at +/-15

• Assuming that the sample will have the specified attribute p% =50 and q%=50

n = p% x q% x [z/e%] ² n= 50.4x 50 x [1.96/15]² n= 42.68

Therefore 43 is the minimum sample size required for the study In our study we have taken 64 as the sample size

(n=32 in continuous infusion Group and n=32 in intermittent bolus Group)

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42

AGE

Age Distribution Continuous Infusion group % Intermittent Bolus Group %

≤ 20 Years 0 0.00 0 0.00

21-30 years 11 34.38 10 31.25

31-40 Years 11 34.38 11 34.38

41-50 years 10 31.25 11 34.38

Total 32 100 32 100

11 11

10 10

11 11

9.4 9.6 9.8 10 10.2 10.4 10.6 10.8 11 11.2

21-30 years 31-40 Years 41-50 years

Number of Subjects

Age Distribution

Continuous Infusion group Intermittent Bolus Group

(45)

43 Age Distribution Continuous Infusion group Intermittent Bolus Group

N 32 32

Mean 34.59 34.31

SD 8.73 8.05

P value

Unpaired t test

0.8939

Majority of the continuous infusion group patients belonged to the 31-40 years age group (n=11, 34.38%) with a mean age of 34.59 years. In the intermittent bolus group patients, majority belonged to the same age group as continuous infusion group (n=11, 34.38%) with a mean age of 34.31 years. The association between the intervention groups and age distribution is considered to be not statistically significant since p >

0.05 as per unpaired t test.

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44

GENDER

Gender Distribution Continuous Infusion group % Intermittent Bolus Group

Male 16 50.00 16 50.00

Female 16 50.00 16 50.00

Total 32 100 32 100

P value

Chi Squared Test

>0.9999

16 16 16 16

0 2 4 6 8 10 12 14 16 18

Male Female

Number of Subjects

Gender Distribution

Continuous In2usion group Intermittent Bolus Group

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45

Majority of the continuous infusion group patients belonged to the male gender group (n=16, 50%). In the intermittent bolus group patients, majority belonged to the male gender group (n=16, 50.00%). The association between the intervention groups and gender distribution is considered to be not statistically significant since p > 0.05 as per chi squared test.

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46

BMI

GROUPS N MEAN SD P

CONTINUOUS INFUSION GROUP

32 24.221 1.1880

0.640

INTERMITTENT BOLUS GROUP

32 24.057 1.2045

The mean BMI was 24.221 in continuous infusion Group and 24.057 in intermittent bolus Group. By conventional criteria the association between the techniques and BMI is considered to be not statistically significant since p > 0.05.

0 5 10 15 20 25 30

continuous infusion intermittent bolus

BMI

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47

Since age, gender, and BMI are not statistically significant it means that there is no difference between the two groups. In other words ,the two group contain subjects with the same basic demographic characteristics.

From the above data, it has been ascertained that there is no significant demographic differences between the two groups. Hence it ensures comparability between the two groups.

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48

ASA

GROUP

ASA I

ASA II

P

VALUE

N % N %

1.00 BY CHI SQUARE TEST CONTINUOUS

INFUSION

15 46.875 17 53.125

INTERMITTENT GROUP

15 46.875 17 53.125

In continuous infusion group, 15 patients belong to ASA I and 17 patients belong to ASA II. In the intermittent group, 15 patients belong to ASA I and 17 patients belong to ASA II.

The data is not statistically significant (p>0.05) and hence the groups are comparable in terms of ASA PS status

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49

PERIOPERATIVE HEART RATE

0 Minutes to 20 minutes

Perioperative Heart rate B.I

A.I (0 min)

5min 10min 15min 20min

Continuous Infusion Group

N 32 32 32 32 32 32

Mean 82.06 82.13 82.56 81.91 81.25 81.09 SD 10.37 10.95 12.94 13.25 13.18 12.43

Intermittent Bolus Group

N 32 32 32 32 32 32

Mean 82.09 84.25 80.19 78.97 77.63 77.78 SD 9.99 9.35 8.28 9.68 10.15 10.42 P value Unpaired t test 0.9902 0.4072 0.3858 0.3155 0.2227 0.2526

82

83 82 81 81

82

84

80 79

78 78

74 76 78 80 82 84 86

B.I A.I (0 min) 5min 10min 15min 20min

Mean HR (bpm)

Perioperative Heart rate

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50

25 Minutes – 1 Hour 15 Minutes

Perioperative Heart rate 25min 30min 40min 50min 1 hr 1.15 hr

N 32 32 32 32 32 32

Mean 81.59 82.03 81.34 81.53 82.22 81.09

SD 13.38 13.88 13.00 13.26 12.51 12.43

N 32 32 32 32 32 32

Mean 79.28 80.88 83.88 82.06 80.19 77.78

SD 10.61 11.06 10.08 10.74 10.26 10.42

P value Unpaired t test 0.2677 0.4467 0.7137 0.3876 0.8608 0.4803

81

82

81

82 82

78 79

81 84 82

80

74 76 78 80 82 84 86

25min 30min 40min 50min 1 hr 1.15 hr

Mean HR (bpm)

Perioperative Heart rate

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51

1 Hour 30 Minutes – 4 Hours

Perioperative Heart rate 1.30 hr 2 hr 2.30 hr 3 hr 3.30 hr 4 hr

N 32 32 32 27 16 32

Mean 82.50 81.88 83.09 83.70 87.25 81.09 SD 13.30 12.05 14.24 13.12 11.54 12.43

N 32 32 32 21 15 32

82

83

82

83

84

87

81

84

82

84

85

88

76 78 80 82 84 86 88 90

1.30 hr 2 hr 2.30 hr 3 hr 3.30 hr 4 hr

Mean HR (bpm)

Perioperative Heart rate

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52

Most of the continuous infusion group patients had mean perioperative heart rates ranging from 82.06 to 81.09 between baseline status and 4 hours perioperatively.

Similarly the intermittent bolus group patients had mean heart rates ranging from 82.09 to 77.08 between baseline status and 4 hours perioperatively. By conventional criteria the association between the intervention groups and perioperative heart rate is considered to be not statistically significant since p > 0.05 as per unpaired t test.

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53

PERIOPERATIVE SYSTOLIC BP

Baseline – 20 Minutes

Perioperative Systolic BP B.I

A.I (0 min)

N 32 32 32 32 32 32

Mean 123.59 126.69 123.50 121.44 119.84 120.16 SD 11.18 8.85 9.38 10.12 10.79 9.80

N 32 32 32 32 32 32

114 116 118 120 122 124 126 128 130 132

BI AI 5min 10min 15min 20min

continuous infusion group intermittent infusion group

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Perioperative Systolic BP 25min 30min 40min 50min 1 hr 1.15 hr

N 32 32 32 32 32 32

Mean 121.16 121.31 124.13 127.22 129.75 119.63 SD 9.32 10.27 10.86 10.04 9.40 21.83

N 32 32 32 32 32 32

114 116 118 120 122 124 126 128 130 132

25min 30min 40min 50min 1hour 1.15hr

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Perioperative Systolic BP

1.30 hr

2 hr

2.30 hr

3 hr

3.30 hr

4 hr

Continuous Infusion Group

N 32 32 32 32 21 15

Mea n

119.91

125.0 6

118.34

124.9 1

122.33

124.8 7 SD 11.50 10.23 11.26 9.22 9.39 9.01

N 32 32 32 32 27 17

Mea n

127.47

126.4 4

126.28

125.5 0

124.89

125.8 8 SD 8.25 9.31 9.75 11.43 11.23 10.90

P value Unpaired t test

0.0038

0.576

0 0.0037

0.819

9 0.3953

0.775 0

112 114 116 118 120 122 124 126 128

1.30hr 2hr 2.30hr 3hr 3.30hr 4hr

continuous infusion group intermittent bolus group

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56

The association between the intervention groups and peroiperative systolic blood pressure is considered to be statistically significant between AI-30 minutes, 1st hour thirty minutes and 2^nd hour thirty minutes since p < 0.05 as per unpaired t test indicating a true difference among intervention groups and the difference is significant. In patients belonging to intermittent bolus intervention group, the systolic blood pressure perioperatively is increased to an average of 128.57 mm Hg between AI-30 minutes, 1st hour thirty minutes and 2^nd hour thirty minutes perioperatively in comparison with patients belonging to continuous infusion intervention group in whom the systolic blood pressure is an average of 121.37 mm Hg with a p-value of <

0.05 according to unpaired t-test. The systolic blood pressure perioperatively was meaningfully less in continuous infusion intervention group compared to intermittent bolus intervention group by 7.19 mm Hg. This significant difference of 1.06 times increase in systolic blood pressure perioperatively in intermittent bolus intervention group compared to continuous infusion intervention group is true and has not occurred by chance. In this study we can safely conclude that Pre operative paravertebral block with continuous infusion of Bupivacaine significantly reduces systolic blood pressure perioperatively compared to Pre operative Paravertebral block with intermittent bolus of Bupivacaine when used in patients undergoing elective thoracotomy surgeries

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Perioperative Mean Arterial Pressure

Perioperative Mean Arterial Pressure B.I

A.I

(0 min)

5min 10min 15min 20min

Continuous Infusion Group

N 32 32 32 32 32 32

Mean 93.18 96.08 93.25 91.81 90.47 90.59

SD 10.78 9.46 9.64 10.53 10.08 9.42

Intermittent Bolus Group

N 32 32 32 32 32 32

Mean 95.58 100.11 97.86 95.92 95.59 95.29

SD 10.35 9.31 9.70 8.99 8.88 8.37

P value Unpaired t test 0.3658 0.0906

0.061 0

0.098 8

0.034 8

0.039 1

85 90 95 100 105

BI AI 5min 10min 15min

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Perioperative Mean Arterial Pressure 25min 30min 40min 50min 1 hr

1.15 hr

N 32 32 32 32 32 32

Mean 95.08 94.52 94.95 94.19 94.08 93.33

SD 8.72 8.48 8.95 8.46 9.31 8.52

N 32 32 32 32 32 32

Mean 91.01 91.52 92.81 94.61 97.04 90.67

SD 9.09 9.86 10.60 9.63 9.32 11.85

P value Unpaired t test 0.0722 0.1967 0.3875 0.8511 0.2087 0.3057

95

95 95

94 94

93

91 92

93

95

97

91 86

88 90 92 94 96 98

Mean MAP (mm Hg)

Perioperative Mean Arterial Pressure

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59

Perioperative Mean Arterial Pressure 1.30 hr 2 hr

2.30 hr

3 hr

3.30 hr

4 hr

N 32 32 32 32 27 16

Mean 93.95 92.96 92.64 92.23 91.43 92.92

SD 9.30 9.62 8.98 10.93 9.97 11.68

N 32 32 32 32 21 15

Mean 92.24 97.23 91.76 97.41 94.49 97.53

SD 9.37 8.90 7.64 7.50 8.23 8.30

P value Unpaired t test 0.4669

0.070 0

0.676 1

0.031 3

0.250 2

0.213 2

94

93 93 92

91

93

92

97

92

97

94

98

88 90 92 94 96 98

1.30 hr 2 hr 2.30 hr 3 hr 3.30 hr 4 hr

Mean MAP (mm Hg)

Perioperative Mean Arterial Pressure

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The association between the intervention groups and peroiperative mean arterial pressure is considered to be statistically significant between 15-20 minutes and at 3 hours since p < 0.05 as per unpaired t test indicating a true difference among intervention groups and the difference is significant. In patients belonging to continuous infusion intervention group, the mean arterial pressure perioperatively is increased to an average of 94.37 mm Hg between between 15-20 minutes and at 3 hours perioperatively in comparison with patients belonging to intermittent bolus intervention group in whom the mean arterial pressure is an average of 92.82 mm Hg with a p-value of < 0.05 according to unpaired t-test. The mean arterial pressure perioperatively was meaningfully more in continuous infusion intervention group compared to intermittent bolus intervention group by 1.55 mm Hg. This significant difference of 1.1 times increase in mean arterial pressure perioperatively in continuous infusion intervention group compared to intermittent bolus intervention group is true and has not occurred by chance. In this study we can safely conclude that Pre operative paravertebral block with continuous infusion of Bupivacaine significantly decreases mean arterial pressure perioperatively compared to Pre operative Paravertebral block with intermittent bolus of Bupivacaine when used in patients undergoing elective thoracotomy surgeries

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PERIOPERATIVE DIASTOLIC BP

Perioperative Diastolic BP B.I

A.I

(0 min)

N 32 32 32 32 32 32

Mean 79.31 84.53 81.75 79.63 79.03 78.97

SD 11.57 10.32 10.57 10.15 9.42 9.41

N 32 32 32 32 32 32

Mean 77.97 80.78 78.13 77.00 75.78 75.81

SD 10.84 10.12 10.39 11.50 11.12 10.23

79 85 82 80 79 79

78 81 78 77 76 76

70 75 80 85 90

B.I A.I (0 min) 5min 10min 15min 20min

Mean DBP (mm Hg)

Perioperative Diastolic BP

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Perioperative Diastolic BP 25min 30min 40min 50min 1 hr 1.15 hr

N 32 32 32 32 32 32

Mean 78.38 77.63 78.25 77.09 77.22 76.81

SD 9.57 9.38 9.96 9.66 10.23 9.54

N 32 32 32 32 32 32

Mean 75.94 76.63 77.16 78.31 80.69 76.19

SD 9.72 10.27 10.90 9.88 9.81 10.10

78

78 77 77 77

76 77

77 78

81

76 72

74 76 78 80 82

Mean DBP (mm Hg)

Perioperative Diastolic BP

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1 Hour 30 Minutes – 4 Hours

Perioperative Diastolic BP 1.30 hr 2 hr 2.30 hr 3 hr 3.30 hr 4 hr

N 32 32 32 32 27 16

Mean 77.19 76.22 75.81 75.59 74.70 76.00

SD 10.68 10.49 9.61 11.45 10.39 13.10

N 32 32 32 32 21 15

Mean 78.41 83.31 78.47 83.66 80.57 83.87

SD 9.09 9.11 7.06 7.60 8.54 8.30

77

76 76 76

75 76

78

83

78

84

81

84

70 72 74 76 78 80 82 84 86

1.30 hr 2 hr 2.30 hr 3 hr 3.30 hr 4 hr

Mean DBP (mm Hg)

Perioperative Diastolic BP

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64

The association between the intervention groups and perioperative diastolic blood pressure is considered to be statistically significant between 2-4 hours since p < 0.05 as per unpaired t test indicating a true difference among intervention groups and the difference is significant. In patients belonging to continuous infusion intervention group, the diastolic blood pressure perioperatively is decreased to an average of 75.67 mm Hg between 2-4 hours perioperatively in comparison with patients belonging to intermittent bolus intervention group in whom the diastolic blood pressure is an average of 81.98 mm Hg with a p-value of < 0.05 according to unpaired t-test. The diastolic blood pressure perioperatively was meaningfully less in continuous infusion intervention group compared to intermittent bolus intervention group by 6.31 mm Hg.

This significant difference of 8% decrease in diastolic blood pressure perioperatively in continuous infusion intervention group compared to intermittent bolus intervention group is true and has not occurred by chance. In this study we can safely conclude that Pre operative paravertebral block with continuous infusion of Bupivacaine significantly decreases diastolic blood pressure perioperatively compared to Pre operative Paravertebral block with intermittent bolus of Bupivacaine when used in patients undergoing elective thoracotomy surgeries